Effects of diazepam, pentobarbital, scopolamine and the timing of saline injection on learned immobility in rats.

The rat forced-swimming test (FST) is widely used for screening substances with a potential antidepressant effect. Rat immobility shown in the FST has been interpreted as "behavioral despair" and has been suggested as an animal model of human depression. In the following series of experiments, it is shown that pentobarbital and scopolamine administered immediately after the first phase, and diazepam administered 15 minutes before the first phase, behave as false positives in the FST. It is concluded that the learning-memory hypothesis seems to cope better with the behavior of rats during the FST than the "behavioral despair" hypothesis. It is also shown that the sensitivity of the FST is affected by the fact that the last saline injection, one hour before the second phase, increases the animals' mobility.